Gardner Syndrome, Turcot Syndrome, familial adenomatous polyposis (FAP) and attenuated FAP are diseases that have been liked to the APC gene. APC is located on the long arm of chromosome 5.
Patients with FAP typically develop hundreds to thousands of colon polyps, usually starting in their teens. Essentially all subjects with FAP will develop colorectal cancer from the colon polyps usually by age 40. Patients with FAP often must have the colon, and sometimes the rectum, removed to prevent colon cancer. A less severe variant of FAP is attenuated FAP.
Gardner syndrome, a variant of FAP, is disease typically characterized by gastrointestinal polyps, multiple osteomas, and skin and soft tissue tumors. Cutaneous findings typically include epidermoid cysts, desmoid tumors, and other benign tumors. Polyps have essentially a 100% risk of undergoing malignant transformation.
Turcot Syndrome is a genetic disease typically characterized by polyps in the colon in addition to tumors in the brain. The polyps in the colon tend to become malignant. The brain tumors are also malignant. There are sometimes also skin abnormalities including cafe-au-lait (coffee-with-milk) spots, multiple lipomas (fatty tumors), and multiple scalp basal cell carcinoma (skin cancers of the scalp). Some consider Turcot syndrome to be a variant of FAP.
A study in mice demonstrated a connection between FAP and insulin-like growth factor II (IGF-II) (Hassan et al., Cancer Res. 60:1070-1076 (2000)). In this study, it was demonstrated that mutation of the IGF-II gene attenuated the expression of the adenomatous phenotype of mice with a mutation in the APC gene.
Presently, there are limited treatment options for patients suffering from FAP and other APC-mediated medical disorders. One of the first medications that was found to shrink colon polyps in patients with FAP was an anti-inflammatory medicine called sulindac. Sulindac is a commonly used nonsteroidal anti-inflammatory drug (NSAID). Many patients, however, cannot tolerate sulindac (e.g., due to gastrointestinal toxicity) and must discontinue taking it. An arthritis medication called celecoxib was approved by the FDA for the treatment of colon polyps in patients with FAP. Celecoxib, however, is a COX-2 inhibitor, and such medications have been linked recently to heart attacks (see e.g., Mukherjee et al., JAMA. 286:954-959 (2001)). Another routine treatment option is the drastic surgical measure of colectomy.
There clearly remains a need in the art for effective treatments of FAP and other APC-related medical disorders.